Silencing of the candidate tumor suppressor gene solute carrier family 5 member 8 (SLC5A8) in human pancreatic cancer

Jong Y. Park, James F. Helm, Weipeng Zheng, Quan P Ly, Pamela J. Hodul, Barbara A. Centeno, Mokenge P. Malafa

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

OBJECTIVES: Few genetic mutations have been identified in pancreatic adenocarcinoma, whereas epigenetic changes that lead to gene silencing are known in several genes. Because SLC5A8 is regarded as a potential tumor suppressor gene that is down-regulated by epigenetic changes in several other cancers, we sought to characterize promoter methylation status and its relationship to SLC5A8 expression in pancreatic cancer. METHODS: Promoter methylation and expression of SLC5A8 were evaluated in pancreatic cancer cell lines, tumor, and adjacent nontumor tissues from pancreatic cancer patients using methylation-specific polymerase chain reaction analysis, quantitative real-time and semiquantitative reverse transcriptase-polymerase chain reaction, and bisulfate-modified sequencing. RESULTS: Complete or partial loss of SLC5A8 expression was observed in all tumor tissues. Bisulfite sequencing analysis on pancreatic cancer cell lines that did not express SLC5A8 detected dense methylation of the promoter region. SLC5A8 expression was reactivated by treatment with aza-deoxycytidine or trichostatin A. Methylation-specific polymerase chain reaction detected methylation in 7 of 10 pancreatic tumor tissues, whereas in only 3 of 28 adjacent nontumor tissues (P < 0.001). CONCLUSIONS: Our findings indicate loss of SLC5A8 expression as a result of aberrant promoter methylation in pancreatic adenocarcinoma. We suggest that SLC5A8 may function as a tumor suppressor gene whose silencing by epigenetic changes may contribute to carcinogenesis and progression of pancreatic cancer.

Original languageEnglish (US)
JournalPancreas
Volume36
Issue number4
DOIs
StatePublished - May 1 2008

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Tumor Suppressor Genes
Pancreatic Neoplasms
Methylation
Epigenomics
Gene Silencing
trichostatin A
Adenocarcinoma
Neoplasms
Deoxycytidine
Tumor Cell Line
Reverse Transcriptase Polymerase Chain Reaction
Genetic Promoter Regions
Real-Time Polymerase Chain Reaction
Carcinogenesis
Cell Line
Polymerase Chain Reaction
Mutation
Genes

Keywords

  • DNA methylation
  • Epigenetic changes
  • Gene silencing
  • Pancreatic cancer
  • SLC5A8
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this

Silencing of the candidate tumor suppressor gene solute carrier family 5 member 8 (SLC5A8) in human pancreatic cancer. / Park, Jong Y.; Helm, James F.; Zheng, Weipeng; Ly, Quan P; Hodul, Pamela J.; Centeno, Barbara A.; Malafa, Mokenge P.

In: Pancreas, Vol. 36, No. 4, 01.05.2008.

Research output: Contribution to journalArticle

Park, Jong Y. ; Helm, James F. ; Zheng, Weipeng ; Ly, Quan P ; Hodul, Pamela J. ; Centeno, Barbara A. ; Malafa, Mokenge P. / Silencing of the candidate tumor suppressor gene solute carrier family 5 member 8 (SLC5A8) in human pancreatic cancer. In: Pancreas. 2008 ; Vol. 36, No. 4.
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abstract = "OBJECTIVES: Few genetic mutations have been identified in pancreatic adenocarcinoma, whereas epigenetic changes that lead to gene silencing are known in several genes. Because SLC5A8 is regarded as a potential tumor suppressor gene that is down-regulated by epigenetic changes in several other cancers, we sought to characterize promoter methylation status and its relationship to SLC5A8 expression in pancreatic cancer. METHODS: Promoter methylation and expression of SLC5A8 were evaluated in pancreatic cancer cell lines, tumor, and adjacent nontumor tissues from pancreatic cancer patients using methylation-specific polymerase chain reaction analysis, quantitative real-time and semiquantitative reverse transcriptase-polymerase chain reaction, and bisulfate-modified sequencing. RESULTS: Complete or partial loss of SLC5A8 expression was observed in all tumor tissues. Bisulfite sequencing analysis on pancreatic cancer cell lines that did not express SLC5A8 detected dense methylation of the promoter region. SLC5A8 expression was reactivated by treatment with aza-deoxycytidine or trichostatin A. Methylation-specific polymerase chain reaction detected methylation in 7 of 10 pancreatic tumor tissues, whereas in only 3 of 28 adjacent nontumor tissues (P < 0.001). CONCLUSIONS: Our findings indicate loss of SLC5A8 expression as a result of aberrant promoter methylation in pancreatic adenocarcinoma. We suggest that SLC5A8 may function as a tumor suppressor gene whose silencing by epigenetic changes may contribute to carcinogenesis and progression of pancreatic cancer.",
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AU - Hodul, Pamela J.

AU - Centeno, Barbara A.

AU - Malafa, Mokenge P.

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N2 - OBJECTIVES: Few genetic mutations have been identified in pancreatic adenocarcinoma, whereas epigenetic changes that lead to gene silencing are known in several genes. Because SLC5A8 is regarded as a potential tumor suppressor gene that is down-regulated by epigenetic changes in several other cancers, we sought to characterize promoter methylation status and its relationship to SLC5A8 expression in pancreatic cancer. METHODS: Promoter methylation and expression of SLC5A8 were evaluated in pancreatic cancer cell lines, tumor, and adjacent nontumor tissues from pancreatic cancer patients using methylation-specific polymerase chain reaction analysis, quantitative real-time and semiquantitative reverse transcriptase-polymerase chain reaction, and bisulfate-modified sequencing. RESULTS: Complete or partial loss of SLC5A8 expression was observed in all tumor tissues. Bisulfite sequencing analysis on pancreatic cancer cell lines that did not express SLC5A8 detected dense methylation of the promoter region. SLC5A8 expression was reactivated by treatment with aza-deoxycytidine or trichostatin A. Methylation-specific polymerase chain reaction detected methylation in 7 of 10 pancreatic tumor tissues, whereas in only 3 of 28 adjacent nontumor tissues (P < 0.001). CONCLUSIONS: Our findings indicate loss of SLC5A8 expression as a result of aberrant promoter methylation in pancreatic adenocarcinoma. We suggest that SLC5A8 may function as a tumor suppressor gene whose silencing by epigenetic changes may contribute to carcinogenesis and progression of pancreatic cancer.

AB - OBJECTIVES: Few genetic mutations have been identified in pancreatic adenocarcinoma, whereas epigenetic changes that lead to gene silencing are known in several genes. Because SLC5A8 is regarded as a potential tumor suppressor gene that is down-regulated by epigenetic changes in several other cancers, we sought to characterize promoter methylation status and its relationship to SLC5A8 expression in pancreatic cancer. METHODS: Promoter methylation and expression of SLC5A8 were evaluated in pancreatic cancer cell lines, tumor, and adjacent nontumor tissues from pancreatic cancer patients using methylation-specific polymerase chain reaction analysis, quantitative real-time and semiquantitative reverse transcriptase-polymerase chain reaction, and bisulfate-modified sequencing. RESULTS: Complete or partial loss of SLC5A8 expression was observed in all tumor tissues. Bisulfite sequencing analysis on pancreatic cancer cell lines that did not express SLC5A8 detected dense methylation of the promoter region. SLC5A8 expression was reactivated by treatment with aza-deoxycytidine or trichostatin A. Methylation-specific polymerase chain reaction detected methylation in 7 of 10 pancreatic tumor tissues, whereas in only 3 of 28 adjacent nontumor tissues (P < 0.001). CONCLUSIONS: Our findings indicate loss of SLC5A8 expression as a result of aberrant promoter methylation in pancreatic adenocarcinoma. We suggest that SLC5A8 may function as a tumor suppressor gene whose silencing by epigenetic changes may contribute to carcinogenesis and progression of pancreatic cancer.

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